REVIEW

Integrating the care of HIV and TB in developing countries

Robin Wood Desmond Tutu HIV Research Centre, Institute of Infectious Disease and Molecular Medicine, UCT Faculty of Health Sciences, Anzio Road, Observatory 7925, South AfricaTel: +27 216 506 806Fax: +27 216 506 963E-mail: Robin.Wood@hiv-research.org.za

part of

Keywords: care, HIV, integration, program, resource-poor, TB

10.2217/14750708.4.6.787 © 2

National TB programs (NTP) in countries with high HIV prevalence have been confronted with increased TB case loads. The complexity of management of TB has been complicated by smear-negative extrapulmonary disease, high mortality and an association with drug-resistant TB. As a result of international funding, access to antiretroviral therapy (ART) has rapidly expanded. NTP and HIV/ART programs have developed separately and HIV/TB patients receive care in two programs, resulting in duplication of care, and missed treatment opportunities. Collaboration between the services has been successfully demonstrated at strategic levels, national surveillance and in small pilot projects at hospital and clinic level. However, streamlining of services alone will not restore TB control in high HIV prevalence settings. HIV/TB control will require both expanded TB program capacity to detect and treat TB cases earlier in order to decrease the infective pool, and HIV services will need to expand ART coverage to decrease the large pool of susceptible individuals in the population.

The HIV epidemic was first recognized in theearly 1980s at a time when TB control was adecreasing priority in developed countries. Theresultant reversal of the decades of declining TBincidence in the USA and a worsening burden ofTB in developing countries [1] led to an increasedinternational prioritization of TB control. TheWHO directly observed short-course therapystrategy (DOTS) was introduced in 1994 andthe first Global Plan to Stop TB initiated in2001 [2]. The Global Plan emphasized access togood-quality, inexpensive TB drugs, togetherwith technical assistance to strengthen existingnational TB control programs [3,4]. Between1990 and 2004, global TB prevalence decreasedfrom 297 to 229 per 100,000. However, TBincidence continued to rise in those countriesmost heavily affected by the HIV epidemic [5].The burden of HIV-associated TB is considera-bly higher than would occur by overlapping ofseparate noninteracting epidemics. This inter-action was manifested by an increased prevalenceof HIV amongst those with active TB disease rel-ative to the general population. In high-TB-burden countries, with greater than 5% adultHIV prevalence, the major proportion of TB(51–57%) is HIV related (Table 1) [4,101]. Whilethe HIV epidemic has been associated withincreased TB rates of smear-positive pulmonarydisease, the HIV-attributable fractions of themore difficult to diagnose smear-negative andextrapulmonary TB disease are markedlyhigher [6]. HIV/TB is also characterized by a

four- to six-fold increased case fatality during TBtherapy [6–8], which is even higher in those withsmear-negative disease [6]. The burden ofHIV/TB disease has been further worsened byincreased rates of TB recurrence followingstandard TB chemotherapy in HIV-infectedindividuals [7,8].

Mycobacterium tuberculosis drug resistance tothe standard chemotherapeutic agents,rifampicin and isoniazid, is widespread.However, the highest prevalences are in low- andmiddle-income countries [9]. Up to 10% ofmultidrug resistance (MDR) cases are infectedwith extensively drug-resistant strains (XDR)that have additional resistance to fluorquinoloneand an injectable second-line drug. XDR exist-ence is a reflection of existing weaknesses in TBcontrol programs [10]. Explosive epidemics ofprimary MDR and XDR infections have beenreported amongst HIV-infected patients [11,12].

The HIV/AIDS epidemic has thereforefuelled TB in areas with highest M. tuberculosistransmission. A total of twelve of the 22 highestTB-burdened countries have a general adultpopulation HIV prevalence of greater than 1%(Table 1) [5,101]. HIV has further strained nationalTB control programs by increasing the totalnumber of TB cases needing treatment, togetherwith an additional complexity of diagnosis andmanagement of smear-negative, extrapulmonaryand drug-resistant TB, all of which are associatedwith high mortality and comorbidity. Althoughthe association between HIV and TB has been

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Table 1. TB burden, strategies for HIV a

Country Pop(n)

India

China

Indonesia

Nigeria

Bangladesh

Pakistan

South Africa

Ethiopia

Phillipines

Kenya

DR Congo

Russia

Vietnam

Tanzania

Brazil

Uganda

Thailand

Mozambique

Myamar

Zimbabwe

Cambodia

Afghanistan

The 22 countries with the hData taken from [5,6].

known almost since the start of the HIV epi-demic, programs to implement collaborativeTB/HIV activities in resource-poor countrieshave been developed only in the past 5 years.With the increasing availability of antiretroviraldrugs, the number of countries that have policiesto implement collaborative TB/HIV activities isincreasing rapidly. The Global Plan to STOPTB, 2006–2015 outlines a framework togetherwith ambitious targets for global TB control.However, the plan acknowledges that these tar-gets are unlikely to be achieved in Eastern Europeand Africa owing to the complexity of managingMDR-TB and HIV/TB coinfection [4]. Thisreview will address the organization of TB andHIV services within a conceptual framework ofTB/HIV interactions.

Barriers to integration of HIV & TB servicesTwo separate disease-management structureshave developed with different characteristicsand very divergent philosophies. National TBprograms (NTP)s have developed over decades,using a centrally organized public-healthapproach. Treatment is strongly tied to popula-tion control of TB transmission, concentratingon standardized diagnosis and chemotherapyof self-referring individuals with predomi-nantly smear-positive pulmonary TB. NTPshave developed pragmatic targets for DOTScoverage, cure rates (>80%) and case finding(70% of smear-positive disease). Medication istypically dispensed daily under direct super-vision for a period of 6–9 months, and is

HIV seroprevalence in general population and TB patients, and national collaborative nd TB testing.

ulation TB incidenceper 100,000

HIV prevalence (%)

HIV%in TB

HIV testing of TB cases

TB testing of HIV cases

1,103,371 168 (107–228) 0.9 (0.5–1.5) 22 In specific groups

Yes

1,315,844 100 (70–130) 0.1 (<0.2) Unk No No

222,781 239 (154–330) 0.1 (0.1–0.2) Unk No No

131,530 283 (147–421) 3.9 (2.3–5.6) 18 Yes No

141,822 227 (165–294) 0.1 (<0.2) 0 No No

157,935 181 (122–246) 0.1 (0.1–0.2) 0 No No

47,432 600 (501–720) 18.8 (16.8–20.7)

52 Yes No

77,431 341 (277–422) (0.9–3.5) 41 Yes No

83,054 291 (79–140) <0.1 (<0.2) Unk No No

34,256 641 (490–806) 6.1 (5.2–7.0) 57 Yes Yes

57,549 356 (262–462) 3.2 (1.8–4.9) 20 Yes No

143,202 119 (102–138) 1.1 (0.7–1.8) Unk Yes Yes

84,238 175 (102–253) 0.5 (0.3–0.9) Unk No No

38,329 342 (269–416) 6.6 (5.8–7.2) 51 No -

186,405 60 (54–73) 0.5 (0.3–1.6) 14 Yes Yes

28,816 369 (295–452) 6.7 (5.7–7.6) 51 Yes Yes

64,233 142 (93–204) 1.4 (0.7–2.1) Unk In specific groups

No

19,792 447 (357–544) 16.1 (12.5–20.0)

Unk No No

50,519 171 (98–246) 1.3 (0.7–2.0) Unk No Yes

13,010 601 (491–729) 20.1 (13.3–27.6)

Unk - -

14,071 506 (335–686) 1.6 (0.9–2.6) 8.2 Yes Yes

29,863 168 (105–229) 0.1 (<0.2) Unk No -

ighest global TB burden.

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usually given at a community level of care.NTPs have successfully made complex TBtreatment scalable and effective.

By contrast, HIV services have developedmore recently and are patient-orientated, with astrong emphasis on human rights and social jus-tice. Individual HIV management is weaklylinked to epidemic disease control, as manyHIV-infected individuals are unaware of theirstatus and are not in care. Antiretroviral therapy(ART) availability in developing countries hasincreased markedly since 2002 as a result ofinternational funding efforts such as the GlobalFund to Fight AIDS, Tuberculosis andMalaria [102] and the Presidents Emergency Pro-gram for AIDS Relief [103]. The rapidity of rollout of ART in many African countries hasresulted in development of ART and HIV careat district levels, where suitable pharmacy andclinical expertise were already available. Indeveloping countries, patients typically enterART programs with very advanced disease andlow CD4 cell counts [13,14], when they are vul-nerable to a wide spectrum of opportunisticinfections including TB [15,16]. ART is a life-long requirement and medication is usually dis-pensed monthly. However, ART is only onecomponent of the required package of HIVcare, as there is a need for diagnosis and treat-ment of a disparate array of opportunistic infec-tions and neoplasms, end-of-life and palliativecare, together with nutritional and social sup-port and the promotion of safe behaviors.HIV/TB management is further complicated bythe need to access medication at bothcommunity and district levels.

Rationale for integration of TB & HIV servicesTB and HIV are intimately intertwined at bothan individual and epidemic level. The burdenof HIV/TB disease on both TB and HIV careservices has been particularly high in develop-ing countries. Large and rapidly growing num-bers of patients with HIV and TB coinfectionrequire coordinated diagnosis, care and treat-ment. HIV/TB cases receive care in two sepa-rate public-health systems, resulting induplication of patient–health provider interac-tions, and the lack of integration between theservices results in missed opportunities for pre-vention and prophylaxis. TB services focus pre-dominantly on smear-positive pulmonarydisease, with the result that HIV-positivepatients with smear-negative pulmonary TB or

extrapulmonary disease can be repeatedlyreferred between HIV and TB services, result-ing in delayed diagnosis, loss to service or evendeath [17].

Proposals for integration of TB and HIV serv-ices have stressed the need for harmonization ofpolicies and planning at a strategic level, includ-ing adaptation of surveillance tools to incorpo-rate both TB and HIV information in HIV andTB registers. National programs have exploredthe adaptation of the existing separate services toinclude the needs of HIV/TB, particularly focus-ing on introducing testing and screening forboth conditions in each service, together withfacilitation of referrals between services. Fullintegration to develop a ‘one-stop shop’ forHIV/TB cases has not been widely advocated;however, such a strategy has been explored inpilot studies [17].

WHO interim recommendations for HIV/TB integrationLarge and rapidly growing numbers of patientswith TB and HIV coinfection require coordi-nated systems for diagnosis, management andsurveillance of HIV/TB. Collaboration and har-monization between national TB and HIV pro-grams, together with some degree of integrationof services at local level, have been advocated bythe WHO.

The WHO has recommended that countries(category I) or districts within countries(category II) that have more than 1% generaladult HIV prevalence enact specific HIV/TBcoordinated initiatives [104]. Recommendedcollaborative activities are focused on threemain areas:

• Establishing HIV/TB coordinating bodies forplanning, surveillance and monitoring

• Decreasing the burden of TB in people livingwith HIV/AIDS by intensified case finding,isoniazid preventive therapy and infectioncontrol in public places

• Decreasing the burden of HIV amongst thosewith TB by provision of HIV testing andcounseling as an entry to care and supportservices, including cotrimoxazole preventativetherapy (CPT) and ART.

Specific global targets were that by 2005, allcategory I and II countries should have estab-lished national coordinating bodies, and that by2007 they should have developed joint TB/HIVimplementation plans and have established HIVsurveillance among TB patients [104].

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Coordination of national TB & HIV control programsNational coordination of TB and HIV activitiesallows for implementation of national surveil-lance and reporting of both HIV status in TBregisters and treatment records and reporting ofTB screening within HIV registers. In 2005, of63 TB/HIV focus countries, 60 provided data tothe WHO indicating that the majority(58–71%) had developed national plans and pol-icies for testing all TB patients for HIV and pol-icies for provision of CPT and ART. However,only 34–41% had policies on intensified TB casefinding, IPT provision and infection controlamong HIV-infected individuals [18]. By 2006,of 22 countries with the highest TB burdens,nine (41%) reported to the WHO that they hadinstituted national HIV/TB coordinating plansthat included universal testing for HIV amongpatients presenting to the TB programs(Table 1) [5,6]. Of the 12 countries with high TBburden together with a general population HIVprevalence of more than 1%, nine (75%) hadinstituted universal testing for HIV infection inTB cases. The number of countries with nationalplans for universal screening for TB among HIVcases was seven (32%) and five (42%) of the 22high-TB burden countries and 12 high-HIV andTB burdens, respectively (Table 1) [4,6].

Integration of TB diagnosis into counseling & testing servicesThe ProTEST initiative was established in 1997by the WHO to explore collaboration betweenHIV/AIDS and TB control programs within sixpilot projects in high HIV prevalence settings inMalawi, South Africa and Zambia [19,20]. Volun-tary counseling and testing (VCT) was the entrypoint to all interventions, and by 2004 more than140,000 people accessed VCT for HIV withinthese projects. Monitoring and evaluation of theprojects did not use standardized definitions,making direct comparisons difficult. All projectsintroduced enhanced HIV prevention strategies;however, the impact of these interventions wasnot measured. Although the provision of isoniazidand cotrimoxazole preventive therapies was shownto be feasible within these collaborative TB/HIVprojects, the uptake of preventive therapy amongeligible clients was low. Symptomatic screeningfor TB in VCT centers, using administration of asymptoms questionnaire, was found to be easy toimplement at little additional cost. Active TB wasidentified on the presence of symptoms in 1–10%of those testing HIV positive [20].

Integration of HIV testing into TB programsThe WHO has reported that TB andHIV/AIDS control programs in most countrieshave begun to respond to the challenge ofHIV/TB [18]. However, the majority of countriesdo not yet have universal HIV testing within TBcontrol programs and low rates of HIV testingare, in most countries, currently the principalobstacle to providing ART to TB patients. Thecoverage of these services in 2005 was far lessthan anticipated by the Global Plan in 2006, thefirst year of its implementation.

Examples of national programs to increaseHIV testing among TB cases have been reportedfrom African countries. In 2004, Rwandanhealth workers who diagnose TB were trained totest confirmed TB cases for HIV infection [21,22].TB monitoring and recording forms were alsomodified to include TB/HIV data. HIV testingof TB cases was reported to increase from 46%of TB patients in 2004 to 81% by the thirdquarter of 2006. In 2005, health staff working indistrict hospitals or clinics of the Kenyan TBcontrol program underwent training to performHIV testing and institute CPT [23]. The nationalTB register was adapted to capture HIV/TBdata, and HIV testing was reported to haveincreased among TB cases from 32% in 2005 to64% by the third quarter of 2006. In Zambia,during 2006, all district and clinic staff weretrained in implementation of national HIV test-ing and counseling guidelines [22]. TB monitor-ing and recording forms were modified tocapture TB/HIV data. Patients were referred toART clinics for CPT. Reported HIV testing inthe Southern Province increased from 2% in2005 to 52% in the third quarter of 2006 [22].

Integration of TB management into HIV home-based careA report on the introduction of DOTS TB careinto an established non-govenmental organiza-tion (NGO) organized home-based care pro-gram in 1998 and 1999, during the pre-ART erain Zambia, illustrated both the potential forintegration at this level of care, together with ahighlighting of some of the difficulties in achiev-ing and evaluating outcomes of such an inter-vention [23]. The intervention consisted of dailyhome visits to HIV/TB-infected individuals forDOTS during the intensive phase of therapy,with a similar comparator population managedat a local TB clinic of the NTP. Recent changesto the NTP made prior to the study period made

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historical comparisons invalid and the compara-tor clinic performance varied during the 2 yearsof the study. High mortality (>20%) at both sitesalso made conventional NTP targets nonachiev-able and the restriction of treatment outcomes toonly smear-positive cases decreased the relevancefor HIV-infected smear-negative and extrapul-monary TB. With extra training, DOTS wasable to be incorporated into home-based care butbecause of the stigma associated with HIV-related home visits, some patients preferred tocontinue daily visits to the TB clinic [23].

Program collaboration strategies for treatment of HIV/TBThere is broad consensus that integrationbetween the TB and HIV programs is desirableto rationalize the care of those with, or at risk of,dual infection [4]. However, the degree of possi-ble integration will depend on factors such asdiffering HIV and TB prevalences, the configu-ration of existing services, available resources andthe ability and willingness of services to adapt.Therefore, there is a spectrum of possible inte-grative strategies, ranging from maintenance oftwo separate programs, with enabling of cross-referrals between services, to full integration,resulting in a single ‘one-stop shop’. Betweenthese two extremes, some mixing of programresponsibilies will result in delivery of TB serv-ices that address HIV needs and HIV servicesthat address TB care.

Collaboration between separate HIV & TB programsMalawi is an example of a country with highburdens of HIV and TB which has maintainedseparate TB and HIV programs [24,25]. Malawihas a population of 12.9, million with morethan 76% living on less than US$2 a day and aper-capita expenditure on health of US$16 dol-lars per annum. There was a fivefold rise in TBnotifications between 1985 and 2000 to an inci-dence rate of greater than 200/100,000(27,000 notified cases per annum), of whom77% are HIV coinfected. The NTB program isbased on WHO-recommended DOTS treat-ment with its own directorate, with central,regional and district tiers responsible for TBcontrol. Case management is by health assist-ants, working within the 44 hospitals treatingTB within the general health service. TB sur-veillance now incorporates HIV testing dataentered into the register by a district TB officer.TB officers are health assistants with little

clinical training and are not qualified to manageother diseases. HIV testing and cotrimoxazoleprophylaxis phased introduction into the TBservice was part of a 2003–2005 TB/HIV plan.In 2005, 47% of TB cases had been tested forHIV, and of the 69% testing HIV positive, 90%started cotrimoxazole.

Nationally, there are close to a million HIV-infected individuals (480,000 to 1.4 million) ofwhom 170,000 are in immediate need of ART.HIV counseling and testing and HIV manage-ment are provided by a separate programmanaged by the Department of Clinical Services.Within this HIV service there has been a rapidexpansion of ART provision. In January 2004,nine facilities provided ART to3000–4000 patients, which was approximately2.4% of the estimated need. By July 2005, 30,055patients had started ART in 60 centers using astandardized approach delivered by clinical offic-ers. A fixed-dose combination of nevirapine/sta-vudine/lamivudine is used by the program.Patients with TB coinfection delay start of ARTfor the first 2 months of TB therapy because ofpossible drug–drug interactions. ART is subse-quently started when the TB continuation phaseof isoniazid and ethambutol is commenced.Mycobacterial culture and drug-sensitivity testingare not performed routinely and the efficacy ofthis regimen for HIV/TB and has not been fullycharacterized. HIV/TB cases can attend the samehospital on the same day but are required toqueue separately for each service.

Integration of HIV/TB treatment & careA pilot project in Durban, South Africa, gives anexample of integration of ART and TB diseasemanagement in an urban setting. The project isbased in a public municipal TB clinic with a caseload in excess of 11,000 new cases of TB perannum. Directly observed TB therapy is pro-vided on site or via a variety in local community-care settings. Concomitant DOT ART and TBwere instituted for coinfected patients usingonce-daily ART during 6–9 months of TB treat-ment, followed by referral to hospital-based ARTcare subsequently. Early results demonstrate rea-sonable on-treatment antiretroviral CD4 andviral suppression results [25].

A similar strategy has been explored in TugelaFerry, at a district hospital serving 300,000 tradi-tional Zulu people in rural KwaZulu-Natal(KZN) [25]. This area suffers some of the highestHIV and TB rates in South Africa, with a poorly

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performing TB control program, manifested bylow treatment-completion rates (59%). In 2001,an HIV clinic was established that providedcotrimoxazole prophylaxis and home-based pal-liative care. An ART program was introduced,and doctors, nurses and community workersreceived training in HIV management. Duringtheir monthly hospital visit, TB/HIV patientsconstruct, under supervision, a months’ supplyof medication to be taken once-daily at home.Adherence is supported by family membersand community treatment workers. After12 months, TB completion rates improved from59 to 83%. Of concern, a high death rateamongst dually infected patients was found to bedue to a high prevalence of a resistant strain ofM. tuberculosis, which appeared to have beenacquired by recent nosocomial or communitytransmission [11].

Full integration of TB and HIV programs at alocal clinic level has been explored in the Khayelit-sha health district of Cape Town, South Africa[20,25]. In 2000, HIV/AIDS clinics were estab-lished in close proximity to the local TB servicesof the South African NTP. In 2001, ART wasadded to the HIV clinic service, which steadilyexpanded to deliver ART to 1400 individuals bySeptember 2005. In 2003, a policy of stepwiseintegration of the two services within the samebuilding was initiated using a common receptionarea. Administration and staff management wasshared, and increased training of each service’sstaff in the other service’s procedures was initiated.Integration of staff from the two services necessi-tated collaboration between five different employ-ing agencies. A uniform patient-centeredapproach was encouraged, using shared medicalfolders incorporating both HIV and TB medicalrecords. During 2003, early assessment of the pro-gram reported HIV testing at TB clinic entry tobe 22%, increasing to 54% at the completion ofTB treatment. TB diagnosis was modified from areliance only on sputum smear by the addition ofmycobacterial culture allowing development of analgorithm for diagnosis of HIV-infected patientswith smear-negative TB. The simplified carepathways demonstrated the potential for service-level integration, but case loads were reported tobe extremely high, resulting in an urgent need fora more streamlined clinic building and improvedmanagement capacity.

Infection controlConcerns have been expressed that integration ofTB and HIV services could result in increased

mixing of TB-infectious and TB-vulnerablepatients with advanced HIV infection, leading toworsening of infection control in resource-poorsettings [26,27]. A large outbreak of XDR-TB inrural South Africa, associated with rapid andnearly universal mortality among HIV patientsreceiving standard TB therapy and antiretrovirals,has highlighted the serious consequences ofhealthcare-associated transmission, which mayhave resulted from breakdown of institutionalinfection control [11].

The cornerstone of infection control in bothintegrated and nonintegrated programs is thecombination of efficient case management,together with minimizing of environment con-tamination. Efficient case management incorpo-rates the early recognition, rapid diagnosis andspeedy institution of appropriate antimyco-bacterial therapy with ongoing monitoring ofresponse to treatment to identify early develop-ment of resistant strains of TB. Without ade-quate diagnostics, however, cases of TB gounrecognized and remain as sources for subse-quent nosochomial transmission. Calls havebeen made for expanded program capacityincluding an expanded global access to sputumculture and drug-sensitivity testing [26]. Mean-while, integrated programs require the develop-ment of a system-wide approach to infectioncontrol, including optimized TB case manage-ment, segregation of active cases, and encour-agement of cough hygiene, together withenvironmental measures. In resource-poor set-tings, technologies such as positive-pressure airconditioning, ultraviolet air cleansing and indi-vidual respiratory protective devices are unavail-able. Environmental control relies on lesstechnically intensive measures, such as separatescheduling of potentially infected patients,cough hygiene, the safe handling of infectioussputum, natural ventilation and the perform-ance of high-risk procedures, such as sputuminduction in the outdoors [28].

Discussion Integration of services at a national strategicplanning level has proved achievable. AlthoughTB and ART programs have very different char-acteristics, most high-burden countries have suc-cessfully set up national bodies to coordinatecollaboration between the services. A majorachievement has been the harmonization ofmonitoring of HIV/TB by incorporation ofinformation on both diseases in HIV and TBregisters in some countries. However, recording

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Executive summary

Barriers to integration

• National TB services– Well established– Centrally organized– Treatment 6–9 mon– Treatment and dise

• HIV services– Rapidly expanding– Patient oriented– Lifelong treatment– Treatment not close

Rationale for integrat

• Strong epidemiologic• Patients require care i• TB diagnosis portal to• HIV/AIDS complicates

WHO interim recomm

• Specific HIV/TB collab• Establishment of natio• Initiate measures to d• Initiate measures to d

Coordination of natio

• In 2005, 57–71% of Htreatment in TB progr

• In 2005, only 34–41%HIV services.

Integration of TB diag

• ProTEST inititiative in • By 2004,140,000 volu• Symptoms questionna

Integration of HIV tes

• Less than 50% of hig• Training of TB officers

rate of HIV testing in

Integration of TB diag

• Directly observed sho• Home visits by HIV se

Program collaboration

• Model of collaboratio• Model of adaptation • Model of full integrat

Infection control

• Epidemic of extensivemixing of infectious T

• Infection control depelacking in resource-po

• There is an urgent ne

of HIV & TB services

thsase control closely linked

ly linked to disease control

ion of TB & HIV services

linkage between diseases.n two services. HIV care. management of TB.

endations for HIV/TB integration

orative activities required if HIV prevalence is more than 1%.nal coordinating bodies by 2007.

ecrease burden of TB in people living with AIDS.ecrease burden of HIV in those with TB.

nal TB & HIV control programs

IV/TB focus countries had implemented policies for HIV testing and provision of cotrimoxazole preventive ams. had implemented policies for intensified TB case finding and isoniazid preventive therapy (IPT) in

nosis into counseling & testing services

Malawi, Zambia and South Africa explored voluntary counseling and testing as entry into HIV/TB care.ntary counseling and testings had been performed.ire identified 1–10% active TB in those testing HIV positive.

ting into TB program

hest-TB-burden countries have instituted universal HIV testing in a TB program. in voluntary counseling and HIV testing (VCT) in Rwanda and Zambia was followed by a doubling in the TB programs.

nosis into HIV home-base care

rt-course therapy strategy TB can be incorporated into home-based care program.rvice staff may be resented owing to stigma.

strategies for treatment of HIV/TB

n between separate HIV and TB programs.of both TB and HIV services to meet needs of coinfected patients. ion of HIV/TB treatment and care.

ly drug-resistant strains in rural populations highlighted concerns of nosochomial spread of TB following B cases with highly susceptible individuals.ndent on efficient case management, but environmental and respiratory protection measures are frequently or settings.

ed for increased access to mycobacterial culture and drug-sensitivity monitoring.

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Discussion

• HIV/TB integration at • Surveillance of HIV/TB

– Integration of servi– HIV/TB case manag– Patients in resource – Wide access to voluCD4 cell counts and r

Executive summary

and reporting remains weak and many of thecountries that have collaborative TB/HIV activi-ties are unable to report fully on recommendedindicators [18]. A further challenge for NTPs ishow to adapt TB control to the needs ofHIV-infected, while maintaining the successes ofTB programs that have been demonstrated inHIV-negative populations. Once diagnosed, thetreatment of TB in both HIV-infected and non-infected has remained standardized. The NTPreliance on passive case finding, sputum smearand existing DOTS targets are, however, less rel-evant for coinfected patients. Symptoms screen-ing has been successfully incorporated into VCTprograms at a low cost per case detected.Increased access to ART has resulted in largenumbers of HIV-infected individuals presentingfor care in resource-constrained settings. Themajority of these patients present with advancedimmune suppression when mortality is high andthere is an urgent need for access to ART and aspectrum of other diagnostic and preventativeservices, which are novel to the staff of the NTP.HIV/TB with advanced immune suppression isill-suited for diagnosis in either of the presentlyconfigured NTP or ART roll-out programs.Further adaptation of existing programs is nec-essary to increase access to culture or other TBdiagnostic modalities.

The challenge of HIV/TB to the ART pro-gram is its protean clinical manifestations thatcan mimic other opportunistic infections (OIs),together with a lack of a sensitive point-of-carediagnostic test. HIV/TB, especially multidrugresistance and extensively drug-resistant strainsstrains, have also exposed the lack of infection-control measures in African health facilities.

While integration of existing TB and HIVtreatment services may streamline health sys-tems, reduce referral delays and improve indi-vidual case management, the integration ofthese services alone is unlikely to be sufficientto control TB at a population level. HIV/TBcomplicates and delays the initiation of ART in

patients with advanced immune suppression.Early initiation of ART soon after a TB diagno-sis may result in drug–drug interactions, pre-cipitate immune restoration disease and resultin an increased pill burden [29]. However, delayin initiation may be associated with high HIVmortality, especially in those with low CD4 cellcounts [30]. These advantages and constraints toearly treatment of coinfected patients are mademore acute because patients are presenting atmuch lower CD4 cell counts in resource-poorcompared with industrialized countries [13,14].Earlier initiation of ART, at CD4 cell countscloser to the guideline threshold of200 cells/mm, will add to ART program case-load, but this strategy may result in a decreasedTB case-load [3]. Program changes will berequired that emphasize earlier identification ofHIV-infected individuals, prior to developmentof symptoms associated with advanced immunesuppression including HIV/TB, with subse-quent access to monitoring of HIV progressiontogether with ongoing active TB case finding.

ConclusionThe HIV epidemic is undermining TB controlin many high TB burden countries. Increasingnumbers of co-infected patients have resulted inlimited collaboration between HIV and TB pro-grams at different levels of the healthcare system.HIV testing of TB cases currently provides amajor portal for entry into HIV care however;HIV testing is still far from universal within TBprograms. Advanced HIV disease makes TB adiagnostic challenge, requiring increased accessto diagnostic modalities additional to sputumsmear. Earlier access to HIV care includingscreening for TB screening will also requireexpansion and reconfiguration of HIV services.

Future perspectiveCollaboration between the existing TB and HIVprograms will increase. However, there will con-tinue to be a need for expanded access to HIV

national planning level has been demonstrated. in high-burden countries is improving:ces alone in high-burden countries is unlikely to restore TB population control ement requires increased access to diagnostics and adaptation of existing programs -poor settings access antiretroviral therapy at very low CD4 cell counts ntary counseling and testing and longitudinal HIV care will allow initiation of antiretroviral therapy at higher educed HIV/TB case load

(cont.)

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counseling and testing outside of these pro-grams. Increased identification of HIV infectionat earlier stages of disease progression will resultin a need for the development of models of lon-gitudinal HIV care. Such programs will incorpo-rate ongoing TB disease screening, allowingdiagnosis and treatment prior to development ofprofound immune suppression. The combina-tion of earlier access to care and improved cover-age of ART will result in a decrease in the highlyTB-susceptible population presently driving theHIV/TB epidemic. Diagnosis of HIV/TB willbe enabled by both new diagnostics and a wideraccess to existing mycobacterial culture, andnucleic acid amplification tests. The increasingrecognition of multidrug resistance and exten-sively drug-resistant strains TB strains will drivethe need to more closely monitor response to

therapy and surveillance for mycobacterialresistance within programs. Improved environ-mental monitoring technologies will allow ear-lier identification of breakdowns in infectioncontrol within busy health facilities and theinstitution of measures to diminish and monitornosochomial transmission.

Financial & competing interests disclosure The author has no relevant affiliations or financialinvolvement with any organization or entity with a finan-cial interest in or financial conflict with the subject matteror materials discussed in the manuscript. This includesemployment, consultancies, honoraria, stock ownership oroptions, expert testimony, grants or patents received orpending, or royalties.

No writing assitance was utilized in the production ofthis manuscript.

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